Developments of small molecules as inhibitors for carbonic anhydrase isoforms

Bioorg Med Chem. 2021 Jun 1:39:116140. doi: 10.1016/j.bmc.2021.116140. Epub 2021 Apr 16.

Abstract

Carbonic anhydrases are ubiquitous, and their role in the hydration of carbon dioxide is essential for the survival of many tissues and organs. However, their association with many pathological diseases, especially in glaucoma, Alzheimer's, obesity, epilepsy, and tumorigenesis, has prompted the design and synthesis of novel carbonic anhydrase inhibitors (CAIs). Herein we describe (1) approaches used in the design of CAIs and (2) synthesis of small molecules as CAIs within the last five years. Despite the active research in this area, there are still more avenues to explore, especially selective inhibition of CA I, CA IX, and XII. These isoforms would continue to open up a diversity of carbonic anhydrase inhibitors containing 1,2,3-triazoles, imidazolone, pyrrolidone, thiadiazole, isatin, and glycoconjugates as part of their molecular frameworks.

Keywords: 1,2,3-traizole; Bioisosterism; Carbonic anhydrases; Erlenmeyer cyclocondensation; Isothermal titration calorimetry; Molecular hybridization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism
  • Catalysis
  • Drug Development*
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Kinetics
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Small Molecule Libraries
  • Carbonic Anhydrases